For many patients, surgical implantation of medical devices can be life-saving. However, implantation of these foreign bodies carries risk of infection. Although the risk of infection of these devices is in general only between 1 and 7%, the consequences of implant-associated infection are of great concern. Implant-associated infections are a major cause of fixation failure and result in increased morbidity, mortality, and treatment cost. The mortality of prosthetic valve endocarditis ranges up to 30%, and mortality rates associated with an infected aortic graft have approached 40%.
A critical step in the pathogenesis of device infections is bacterial adherence to the foreign body surface and the formation of a bacterial biofilm. A biofilm is defined as a structured community of bacterial cells enclosed in a self-produced polymeric matrix and adherent to an inert or living surface. Biofilms are characterized by high concentrations of organisms with little turnover and low metabolic activity. Bacteria within the biofilm communicate with each other through the elaboration and recognition of small molecules, a process called “quorum sensing”. In orthopedic trauma for example, some 5-10% of orthopedic hardware facilitates host infection with increasing incidences for open fractures, combat related injuries, and revision joint replacements. As more soldiers from current armed conflicts around the globe survive serious blast trauma due to improved body armor, many sustain debilitating and life-threatening wound-related infections. Thus the need for improved implant surface protection in both civilian and military trauma patients has spurred recent research.
In the past, localized antimicrobial delivery systems have been developed for the treatment and prevention of implant-associated infections, including poly(methylmethacrylate) cements, biodegradable polymers, and regional limb perfusions. The elution kinetics of antimicrobials from these carrier systems typically exhibit an initial supra-therapeutic release that ultimately drops below the minimal inhibitory concentration (MIC). Such sub-MIC antimicrobial levels favor the emergence of drug-resistant bacterial strains. In addition, antimicrobials are typically ineffective in penetrating biofilms and may trigger quorum sensing and altered gene expression.
In the field of Ear Nose and Throat (ENT), for example, 8 out of 16 “failed” osteointegrating screws were found to have biofilm as determined by scanning electron microscopy (SEM). (Monksfiled P, Chapple I et al. J Laryngol Otol 125; 2011). Children undergoing treatment for otitis media, at an estimated cost of greater than $5 billion annually and a demographic distribution in the United States of 83% of children, will have at least one episode post-tympanostomy tube otorrhea, with 16% early postoperative, 26% late postoperative, 4% chronic and 7% recurrent. Fluorocarbon and silicone polymers constitute some of the substrates of tympanostomy tubes which are susceptible to bacterial adhesion.
The “Biofilm Hypothesis” states that persistent bacterial infection in the absence of positive culture and recalcitrance to antibiotic treatment is at the core of the failure of systemic therapies. In general the most common treatment for any implant infection today is re-operation, often requiring staged surgical interventions to clean or exchange the implant, debridement of infected tissues, followed by antimicrobial therapy, in some cases for several years.
In the United States alone, at least 100,000 out of over two million fixation device implants result in some form of postoperative infection. The cost of treating an implant-associated infection ranges from $30,000 to $300,000 and often involves repeated hospitalizations for treatment. Despite concerted efforts to resolve infections, there remains a very high rate of failure associated with initial infection treatment. Commonly, first course failure approaches 30% and results in a high rate of second and third course failure, multiplying costs and often leading to an ex-plant of the fixation device.
There exists a need for improved coatings that inhibit or prevent biofilm formation on implants, including orthopedic and dental implants, implants for ear, nose, and throat applications, and cardiovascular devices.
There also exists a need for improved coatings that inhibit or prevent biofilm formation on implants designed for long term implantation and/or decrease healing times in vivo in the presence of infection or other complications, e.g., open contaminated wounds and infections or closed wounds at risk for infection.
Therefore, it is an object of the invention to provide improved coatings for biomedical implants that inhibit or prevent biofilm formation.
It is also an object of the invention to provide improved coatings for implants that decrease healing times in vivo in the presence of infection or other complications, e.g., open contaminated wounds and infections or closed wounds at risk for infection.